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Z. Li, S.P. Mahesh, B. Liu, D. Shen, C.–C. Chan, I. Pastan, R.B. Nussenblatt; Eradication of Tumor Colonization and Invasion by a B Cell Specific Immunotoxin in a Murine Model for Human Primary Intraocular Lymphoma (PIOL) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2828.
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© ARVO (1962-2015); The Authors (2016-present)
Human primary intraocular lymphoma (PIOL) is a malignant disease with few effective therapies available. Most cases are B cell in origin, and there is currently a need for animal model(s) permitting the investigation of the molecular pathogenesis of the disease and the evaluation of new therapeutic approaches. This study is aimed to establish a better mouse model to closely mimic human PIOL and to test the therapeutic potentials of a recently developed immunotoxin targeting human B cells.
A murine model that mimics human primary intraocular lymphoma (PIOL) was established by injecting human B cell lymphoma cells intravitreously into SCID mice. The resemblance of this model to human PIOL was examined by fundoscopy, histopathology, immunohistochemistry, and molecular biological markers. The therapeutical effectiveness of immunotoxin HA22 was tested by injecting the drug intravitreously.
The murine model resembles human PIOL closely. Pathological examination revealed that the tumor cells were initially colonizing on the retina surface, followed by infiltrating through the retina layers and penetrating the retinal pigment epithelium (RPE). Tumor metastasis into the central nervous system was also observed in the animals with long standing disease. B cell specific immunotoxin was used to treat this lymphoma. A single intravitreal injection of the immunotoxin after the establishment of the PIOL successfully abrogated the further development of the malignancy.
This is the first report of a murine model that closely mimics human B cell PIOL. This model may be a valuable tool in understanding the molecular pathogenesis of human PIOL and the evaluation of new therapeutic approaches. The results of B cell specific immunotoxin therapy may have clinical implications in treating human PIOL.
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